Early Changes in Cardiac Macrophage Subsets in Heart Failure with Preserved Ejection Fraction

Area of Science:

• Cardiovascular Research
• Immunology
• Pathophysiology

Background:

• Heart failure with preserved ejection fraction (HFpEF) is linked to inflammation and diastolic dysfunction.
• Cardiac macrophages are implicated in the progression of HFpEF.
• Understanding macrophage dynamics is crucial for HFpEF pathogenesis.

Purpose of the Study:

• To characterize cardiac macrophage subsets during the progression of experimental HFpEF.
• To investigate the association between macrophage phenotypes and early HFpEF development.

Main Methods:

• A mouse model of HFpEF was induced using a high-fat diet and L-NAME.
• Cardiac macrophage populations (CCR2+, CCR2-) were analyzed at preclinical (5 weeks) and established (15 weeks) HFpEF stages.
• Measurements included metabolic biomarkers, blood pressure, cardiac function, inflammation markers, and AMPK activity.

Main Results:

• Preclinical HFpEF showed decreased resident reparative CCR2-MHCII- macrophages and increased proinflammatory CCR2+MHCII+ macrophages.
• These early macrophage shifts correlated with increased TNF-α, reduced AMPK activation, and fibrosis.
• Established HFpEF maintained elevated proinflammatory macrophages, while resident macrophages initially decreased then recovered.

Conclusions:

• Early alterations in cardiac macrophage profiles precede HFpEF onset in this model.
• The shift from reparative to proinflammatory macrophages is associated with inflammation and cardiac remodeling in HFpEF.
• Targeting these early macrophage changes may offer therapeutic strategies for HFpEF.